Research in the Cell Signaling and Developmental Pharmacology Program focuses on signaling pathways and how they impact on cancer progression, therapy and management of complications. The overall goals of the members of this program are to understand fundamental cell signaling events in malignant cells and apply this understanding to the development of new agents or novel therapeutic regimens for the treatment of cancer. There are two themes within the Program's research. Theme 1 - Understanding fundamental cell signaling events that regulate malignant cell behavior Theme 2 - Translational and clinical trials of novel agents or novel combinations of agents Investigators in the Cell Signaling and Developmental Pharmacology Program have made a number of discoveries that have significant clinical implications. For example, they have contributed significantly to (a) our understanding of how isoprenoid intermediates in the mevalonic acid to cholesterol pathway regulate expression of RAS and RAS-related small GTPases, (b) that bisindoylmalemimide IX can override the apoptosis-inhibitory effects of Bcl-2 and (c) studies exploring innovative clinical regimens for a variety of cancers. There are numerous past and present productive collaborations both between members of the Program, and with members of other Cancer Center programs. The Cell Signaling and Developmental Pharmacology Program consists of 38 members from 17 departments in 4 colleges. Peer-reviewed, direct research funding for this program totals $3,825,705, with $1,213,571 of this support coming from the NCI.